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O00337 (S28A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/nucleoside cotransporter 1
Alternative name(s):
Concentrative nucleoside transporter 1
Short name=CNT 1
Short name=hCNT1
Na(+)/nucleoside cotransporter 1
Sodium-coupled nucleoside transporter 1
Solute carrier family 28 member 1
Gene names
Name:SLC28A1
Synonyms:CNT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length649 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine). It also transports the antiviral pyrimidine nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immunodeficiency syndrome (AIDS). It has the following selective inhibition: adenosine, thymidine, cytidine, uridine >> guanosine, inosine.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in kidney.

Polymorphism

Three variant forms of isoform 1 (A, B and C) are expressed in the kidney. All three variant forms have similar nucleoside transport activity.

Sequence similarities

Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family. [View classification]

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00337-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O00337-2)

The sequence of this isoform differs from the canonical sequence as follows:
     155-175: GLALAAFLGLVLWLSLDTSQR → DPRPWSKEGPNQYLPQITWTV
     176-649: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 649649Sodium/nucleoside cotransporter 1
PRO_0000070446

Regions

Topological domain1 – 8080Cytoplasmic Potential
Transmembrane81 – 10424Helical; Potential
Topological domain105 – 1095Extracellular Potential
Transmembrane110 – 12819Helical; Potential
Topological domain129 – 14719Cytoplasmic Potential
Transmembrane148 – 16720Helical; Potential
Topological domain168 – 17811Extracellular Potential
Transmembrane179 – 19517Helical; Potential
Topological domain196 – 2016Cytoplasmic Potential
Transmembrane202 – 22221Helical; Potential
Topological domain223 – 26139Extracellular Potential
Transmembrane262 – 28322Helical; Potential
Topological domain284 – 29411Cytoplasmic Potential
Transmembrane295 – 31824Helical; Potential
Topological domain319 – 33719Extracellular Potential
Transmembrane338 – 36023Helical; Potential
Topological domain361 – 3666Cytoplasmic Potential
Transmembrane367 – 38620Helical; Potential
Topological domain387 – 42337Extracellular Potential
Transmembrane424 – 44623Helical; Potential
Topological domain447 – 45711Cytoplasmic Potential
Transmembrane458 – 47922Helical; Potential
Topological domain480 – 53455Extracellular Potential
Transmembrane535 – 55824Helical; Potential
Topological domain559 – 56911Cytoplasmic Potential
Transmembrane570 – 59223Helical; Potential
Topological domain593 – 64957Extracellular Potential
Compositional bias609 – 6124Poly-Ser

Amino acid modifications

Glycosylation6051N-linked (GlcNAc...) Potential
Glycosylation6431N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence155 – 17521GLALA…DTSQR → DPRPWSKEGPNQYLPQITWT V in isoform 2.
VSP_037221
Alternative sequence176 – 649474Missing in isoform 2.
VSP_037222
Natural variant341E → G in A. Ref.1 Ref.2
VAR_009499
Natural variant1401L → LV in A. Ref.1 Ref.5
VAR_009500
Natural variant1891V → I in A. Ref.1 Ref.3
Corresponds to variant rs2290272 [ dbSNP | Ensembl ].
VAR_009501
Natural variant1901A → S.
Corresponds to variant rs45523532 [ dbSNP | Ensembl ].
VAR_057194
Natural variant2371Q → K.
Corresponds to variant rs8187758 [ dbSNP | Ensembl ].
VAR_057195
Natural variant4091N → S in B. Ref.1
VAR_009502
Natural variant5101R → C. Ref.5
Corresponds to variant rs2242047 [ dbSNP | Ensembl ].
VAR_057196
Natural variant5211D → N in B and C. Ref.1 Ref.3
Corresponds to variant rs2242046 [ dbSNP | Ensembl ].
VAR_009503
Natural variant5461S → P.
Corresponds to variant rs45584739 [ dbSNP | Ensembl ].
VAR_061802

Experimental info

Mutagenesis3181S → G: Enables transport of purine nucleosides. Ref.6
Mutagenesis3191Q → M: Increases transport of purine nucleosides; when associated with Gly-319. Ref.6
Mutagenesis3521S → T: Produces a full purine-type transporter; when associated with Gly-319 and Met-320. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: 42E952443B46B102

FASTA64971,584
        10         20         30         40         50         60 
MENDPSRRRE SISLTPVAKG LENMGADFLE SLEEGQLPRS DLSPAEIRSS WSEAAPKPFS 

        70         80         90        100        110        120 
RWRNLQPALR ARSFCREHMQ LFRWIGTGLL CTGLSAFLLV ACLLDFQRAL ALFVLTCVVL 

       130        140        150        160        170        180 
TFLGHRLLKR LLGPKLRRFL KPQGHPRLLL WFKRGLALAA FLGLVLWLSL DTSQRPEQLV 

       190        200        210        220        230        240 
SFAGICVFVA LLFACSKHHC AVSWRAVSWG LGLQFVLGLL VIRTEPGFIA FEWLGEQIRI 

       250        260        270        280        290        300 
FLSYTKAGSS FVFGEALVKD VFAFQVLPII VFFSCVISVL YHVGLMQWVI LKIAWLMQVT 

       310        320        330        340        350        360 
MGTTATETLS VAGNIFVSQT EAPLLIRPYL ADMTLSEVHV VMTGGYATIA GSLLGAYISF 

       370        380        390        400        410        420 
GIDATSLIAA SVMAAPCALA LSKLVYPEVE ESKFRREEGV KLTYGDAQNL IEAASTGAAI 

       430        440        450        460        470        480 
SVKVVANIAA NLIAFLAVLD FINAALSWLG DMVDIQGLSF QLICSYILRP VAFLMGVAWE 

       490        500        510        520        530        540 
DCPVVAELLG IKLFLNEFVA YQDLSKYKQR RLAGAEEWVG DRKQWISVRA EVLTTFALCG 

       550        560        570        580        590        600 
FANFSSIGIM LGGLTSMVPQ RKSDFSQIVL RALFTGACVS LVNACMAGIL YMPRGAEVDC 

       610        620        630        640 
MSLLNTTLSS SSFEIYQCCR EAFQSVNPEF SPEALDNCCR FYNHTICAQ 

« Hide

Isoform 2 [UniParc].

Checksum: 34C7DD93D84F60EE
Show »

FASTA17520,180

References

« Hide 'large scale' references
[1]"Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1)."
Ritzel M.W.L., Yao S.Y.M., Huang M.-Y., Elliott J.F., Cass C.E., Young J.D.
Am. J. Physiol. 272:C707-C714(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS A GLY-34; VAL-140 INS AND ILE-189, VARIANTS B SER-409 AND ASN-521, VARIANT C ASN-521.
Tissue: Kidney.
[2]"Genomic organization and sequence of the gene encoding the human sodium-dependent, pyrimidine-selective nucleoside transporter (CNT1)."
Ritzel M.W.L., Ritzel R.G., Cass C.E., Young J.D.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT A GLY-34.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT A ILE-189, VARIANT B ASN-521, VARIANT C ASN-521.
Tissue: Small intestine.
[4]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS A VAL-140 INS AND CYS-510.
Tissue: Colon.
[6]"Identification of amino acid residues responsible for the pyrimidine and purine nucleoside specificities of human concentrative Na(+) nucleoside cotransporters hCNT1 and hCNT2."
Loewen S.K., Ng A.M.L., Yao S.Y.M., Cass C.E., Baldwin S.A., Young J.D.
J. Biol. Chem. 274:24475-24484(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-318; GLN-319 AND SER-352.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U62966 mRNA. Translation: AAB53837.1.
U62967 mRNA. Translation: AAB53838.1.
U62968 mRNA. Translation: AAB53839.1.
AF187978 expand/collapse EMBL AC list , AF187969, AF187970, AF187971, AF187972, AF187973, AF187974, AF187975, AF187976, AF187977 Genomic DNA. Translation: AAF15353.1.
AK291997 mRNA. Translation: BAF84686.1.
AC087468 Genomic DNA. No translation available.
AC103741 Genomic DNA. No translation available.
BC029788 mRNA. Translation: AAH29788.1.
BC039898 mRNA. Translation: AAH39898.1.
BC126204 mRNA. Translation: AAI26205.1.
BC126206 mRNA. Translation: AAI26207.1.
RefSeqNP_001274691.1. NM_001287762.1.
NP_004204.3. NM_004213.4.
NP_964014.1. NM_201651.2.
XP_005255046.1. XM_005254989.2.
XP_005255048.1. XM_005254991.2.
UniGeneHs.459187.

3D structure databases

ProteinModelPortalO00337.
SMRO00337. Positions 179-590.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000286749.

Chemistry

BindingDBO00337.
ChEMBLCHEMBL5551.

Protein family/group databases

TCDB2.A.41.2.3. the concentrative nucleoside transporter (cnt) family.

PTM databases

PhosphoSiteO00337.

Proteomic databases

PaxDbO00337.
PRIDEO00337.

Protocols and materials databases

DNASU9154.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286749; ENSP00000286749; ENSG00000156222. [O00337-1]
ENST00000338602; ENSP00000341629; ENSG00000156222. [O00337-2]
ENST00000394573; ENSP00000378074; ENSG00000156222. [O00337-1]
GeneID9154.
KEGGhsa:9154.
UCSCuc002blf.3. human. [O00337-2]
uc002blg.3. human. [O00337-1]

Organism-specific databases

CTD9154.
GeneCardsGC15P085427.
HGNCHGNC:11001. SLC28A1.
HPAHPA019551.
MIM606207. gene.
neXtProtNX_O00337.
PharmGKBPA387.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1972.
HOVERGENHBG054073.
InParanoidO00337.
KOK11536.
OMAIMVPETE.
OrthoDBEOG7RV9FR.
PhylomeDBO00337.
TreeFamTF314131.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO00337.
BgeeO00337.
CleanExHS_SLC28A1.
GenevestigatorO00337.

Family and domain databases

InterProIPR008276. C_nuclsd_transpt.
IPR018270. C_nuclsd_transpt_met_bac.
IPR011657. Nucleos_tra2_C.
IPR011642. Nucleoside_recog_Gate.
IPR002668. Nuclsd_transpt2.
[Graphical view]
PANTHERPTHR10590. PTHR10590. 1 hit.
PfamPF07670. Gate. 1 hit.
PF07662. Nucleos_tra2_C. 1 hit.
PF01773. Nucleos_tra2_N. 1 hit.
[Graphical view]
TIGRFAMsTIGR00804. nupC. 1 hit.
ProtoNetSearch...

Other

GeneWikiConcentrative_nucleoside_transporter_1.
GenomeRNAi9154.
NextBio34343.
PROO00337.
SOURCESearch...

Entry information

Entry nameS28A1_HUMAN
AccessionPrimary (citable) accession number: O00337
Secondary accession number(s): A0AV42 expand/collapse secondary AC list , A8K7I2, O00335, O00336, Q5U5S6, Q5U648, Q9UEZ9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 5, 2009
Last modified: April 16, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM